Natural tissue bioimplants are gaining acceptance as advantageous alternatives to synthetic implants in many surgical procedures. Among other advantages, bioimplants more closely resemble in size, shape and performance the biological structures that they are designed to replace than do synthetic implants. Thus bioimplants are, in many circumstances, considered the devices of choice for replacement or structural augmentation of internal tissues and organs.
The sources of bioimplants include non-human and human donors. In general, the choice of donor depends on a number of factors, including the relative sizes of the donor and recipient. For example, as an alternative to a human cadaver, a sheep, pig, cow or horse may serve as a donor. In some cases, the donor and recipient may be the same. Immunogenic limitations are overcome by crosslinking the tissues to mask antigenic molecules in the tissue. Sterilization is generally effected by contacting the tissue with a chemical sterilizing agent. In many cases, crosslinked and sterilized bioimplants provide many of the features of natural tissue, while avoiding to a great degree the problem of xeno-tissue rejection that is characteristic of live tissue implantation.
In many cases, bioimplants provide additional advantages over synthetic implants. For example, many bioimplants permit infiltration of the recipient's own cells into the bioimplant. In particular, the infiltrating cells can use the bioimplant as a template or scaffold for re-constructing organ or tissue structures comprising the recipient's own cells. In some cases, all or part of the bioimplant can be replaced by the recipient body's own cells. This process, which is referred to as remodeling, is advantageous in that it can improve the integration of the bioimplant into the implant site. Due to these advantages, it is considered advantageous to promote remodeling of bioimplant tissue.
While some bioimplants can stimulate remodeling by themselves due to their natural origin and their possession of a collagen matrix that acts as a scaffold for tissue regrowth, it is sometimes considered advantageous to stimulate remodeling by administering to a bioimplant recipient one or more agents that stimulate tissue growth. For example, bone morphogenic proteins (BMPs) have been used experimentally to promote bone regrowth in spinal fusion surgery. For example, a resorbable collagen sponge infused with recombinant bone morphogenic protein-2 (rhBMP-2) has been approved for use in spinal surgery. It is believed that release of rhBMP-2 from the sponge stimulates osteoblast infiltration, proliferation and organization. As the collagen sponge is resorbable, eventually regrown host tissue replaces the sponge. The use of the rhBMP-2 infused collagen sponge in spinal surgery has been credited with greatly reducing the failure rate of spinal surgery.
Despite the improvements in surgical outcomes that have already been provided by growth factor infused bioimplants, many challenges remain to be overcome. For example, infusion of bioimplants is only useful where the bioimplant is absorbent, that is where soaking of the tissue in a solution containing the growth factor results in there being enough growth factor infused into the tissue to stimulate tissue growth after it has been implanted into a recipient. Thus, the infusion method is not considered effective for less porous bioimplant devices such as heart valves, skin grafts, tendon, bone and ligament repair tissues, etc. Another limitation is that release of the growth factor is by diffusion. While diffusion can in some instances be a useful method of release, in other circumstances diffusion may result in too high an initial rate of release and thus too low a later rate of release. Thus, one disadvantage of diffusive release is that the effective release period may be shorter than desired, unless excess growth factor is infused into the bioimplant at the start. However, this may not always be feasible or even possible. Moreover, even if it were possible to infuse excess growth factor into the bioimplant, a disadvantage arising out of this approach may be that the local concentration of growth factor may cause diffusion of the growth factor into surrounding tissue, including capillaries, veins and arteries, where it may bring about deleterious local or systemic effects. In some cases, such diffusion may even give rise to new tissue growth in an area distal to the area where new growth is desired.
There is thus a need for a device that overcomes the limitations of the prior art growth factor infused collagen sponge. There is a need for a bioimplant device that is capable of delivering growth factor to a desired area, wherein the growth factor is released from the bioimplant device at a rate that is less than the diffusive rate of release from the prior art growth factor-infused collagen sponge. There is likewise a need for a bioimplant device that has associated with it a growth factor that is subject to degradation of the growth factor to a lesser degree than is the growth factor-infused collagen sponge of the prior art. There is also a need for a bioimplant device that has associated with it a growth factor that is covalently bonded to the bioimplant. There is likewise a need for processes of making such bioimplant devices. These and other needs are met by embodiments of the invention.
There is also a need for a bioimplant device that carries an adjunct. There is also a need for a bioimplant device that is capable of delivering an adjunct to a desired area, wherein the adjunct is released from the bioimplant at a rate that is less than the diffusive rate of release of the adjunct from an infused collagen sponge. There is likewise a need for a bioimplant device that has associated with it an adjunct that is subject to degradation to a lesser degree than an adjunct in an adjunct-infused collagen sponge. There is also a need for a bioimplant device that has associated with it an adjunct molecule that is covalently bonded to the bioimplant. There is likewise a need for processes of making such bioimplant devices. These and other needs are met by embodiments of the invention.